Semaglutide improves physical limitations and exercise function in patients of HFpEF with Obesity phenotype regardless of LVEF

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, shows promise in the treatment of heart failure patients with the obesity phenotype of heart failure with preserved ejection fraction (HFpEF), according to the STEP-HFpEF trial. The study found that semaglutide's benefits in improving symptoms, exercise capacity, and weight were consistent across different left ventricular ejection fraction (LVEF) categories. The results also revealed no safety concerns at any LVEF level. This suggests that semaglutide could be a valuable treatment option for HFpEF patients, regardless of their baseline LVEF.

This study was published in the Journal Of The American College Of Cardiology by Butler J. and colleagues. The STEP-HFpEF trial enrolled 529 patients who had a body mass index of 30 kg/m² or greater and were free from diabetes. Participants had varying LVEFs of 45% or greater and exhibited characteristics associated with HFpEF. They were randomly assigned to receive once-weekly subcutaneous semaglutide 2.4 mg or a placebo in addition to standard care.

The primary outcome measured was radiologically verified recurrent hiatal hernia occurring more than 10 years after the initial surgery. Secondary outcomes included dysphagia scores for solid and liquid foods, generic health survey scores, gastrointestinal symptom assessment scores, proton pump inhibitor consumption, and reoperation rates.

• Out of 145 available patients, 103 participated in the long-term follow-up, with a mean age of 65 years.
• After a mean follow-up time of 13 years, the study found that the radiologically verified hiatal hernia recurrence rates were 38% in the mesh group compared to 31% in the suture group, with no significant difference between them.
• However, 13 years postoperatively, patients who had undergone mesh repair reported significantly higher dysphagia scores for solid foods, suggesting greater difficulty swallowing.

The results of the long-term analysis of the STEP-HFpEF trial indicate that semaglutide, a GLP-1 receptor agonist, provides consistent benefits to HFpEF patients with the obesity phenotype across different LVEF categories. This suggests that semaglutide may be a valuable therapeutic option, regardless of the patient's baseline LVEF. Moreover, the trial demonstrated no safety concerns in patients with the lowest EFs, supporting the use of semaglutide in HFpEF. However, further research is needed to understand the drug's mechanisms fully and explore its effects on clinical outcomes, such as mortality and hospitalizations for heart failure.

Reference:

Butler J, Abildstrøm SZ, Borlaug BA, et al. Semaglutide effects according to ejection fraction in heart failure with preserved ejection fraction and obesity. J Am Coll Cardiol. 2023;Epub ahead of print